Human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). At present there is no effective vaccine against this disease and therapeutic agents provide only limited help. this objects of this project are to characterize HIV antigens, determine the targets of humoral and cell-mediated immunity, and to use this information to develop candidate vaccines. We have constructed recombinant vaccinia viruses containing HIV genetic information. These viruses have been used as live experimental vaccines to immunize animals, to synthesize HIV proteins in tissue culture, to make targets for cytotoxic T cells, and study CD4-envelope protein interactions. A detailed kinetic and quantitative analysis of the early and late biosynthetic events undergone by the HIV-1 envelope glycoprotein expressed by a recombinant vaccinia virus was made. Studies with the drug brefeldin A suggested that assembly of gp160 into oligomers occurs in a post-golgi compartment. Chemical cross-linking, sucrose gradient sedimentation and polyacrylamide gel electrophoresis revealed that the HIV-2 envelope protein also assembles postranslationally into dimers and higher oligomers. The effects of C- terminal and internal deletions of the HIV-1 envelope protein on synthesis, transport, biological properties, and antigenicity were determined. The predominant conserved B cell epitopes were mapped to gp41 and the C- terminus of gp120 whereas cytotoxic T epitopes were distributed throughout the length of the glycoprotein. A new protease inhibitor was shown to block maturation of human and simian immunodeficiency viruses and spread of infection.